We have used a reverse genetic approach to investigate this question and created conditional knockout mice with reduced mtDNA expression in midbrain DA neurons. These mice have adult onset of slowly progressive, typical parkinsonian symptoms accompanied by progressive formation of intracellular inclusions and characteristic neuropathology. The inclusions are present in most DA neurons and contain both mitochondrial membranes and proteins. Our findings thus support an etiological role for respiratory chain dysfunction Parkinsons disease and suggest a novel mechanism for the formation of Lewy bodies.